Formate esters

ABSTRACT

1. THE DIFORMATE FRACTION OF IMPRIRICAL FORMULA C1H16O4 OBTAINED BY THE REACTION OF CYCLOOCTA-1,5-DIENE WITH FORMALDEHYDE OR PARAFORMALDEHYDE IN THE PRESENCE OF FORMIC ACID, SAID FRACTION HAVING A BOILING POINT OF 90-110* C./0.05 TO 0.2MM. HG, A DENSITY OF 1.1-1.2 G/ML. AT 22* C., AND REFRACTIVE INDEX 1.47-1.50 AT 21*C. IN THE D LINE OF SODIUM.

March 28, 1972 J HEYWQOD ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21, 1966 14 Sheets-Sheet 1 Q n g Q Q g m N- E a? g E Q ca o Q (n W 2 3 Q Q o 2 5 5 \1 v LO QOUDII/LUSUDJ] March 28, 1972 B J HEYWQQD ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21. 1966 14 Shoots-Sheet 2 42 40 383634 32 3028 2624 22 20 78 76 I4 72 70 retent/on time minutes March 28, 1972 J w ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21, 1966 r 14 Sheets-Sheet s 2000 7800 7600 1400 1200 1000 800 650 wavenumber aoumywsuzw March 28, 1972 a HEywooD EIQAL 3,652,656

FORMATE ESTERS l4 Shuts-Sheet 4 Filed Nov. 21, 1966 March 28, 1972 B, HEYWOOD ETAL 3,652,656

FORMATE ESTERS 14 Shuts-Shoat 5 Filed Nov. 21, 1966 March 28, 1972 HEYWOQD ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21, 1966 14 Sheets-Sheet 6 FIG. 6.

' retentiontime -m/'nutes March 28, I972 1 HEYWQOD ETAL 3,652,656

FORMATE ESTERS l4 Sheets-Shut 7 Filed Nov. 21, 1966 cmm Q LmnEac uk Q8 QQN DOE QQQ QQQ QQQ DOOM QQQv $8M DD O av Q9 m w m W mrvimzs m m R m m mm March 28, 1972 HEYWQQD ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21, 1966 14 Shoots-Sheet 8 FIG. 8.

March 26, 1972 B. J. H EYWOOD ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21. 1966 14 Sheets-Sheet 9 L 8 05 (D C 6% Q3 8 Q m 5 5" a I Q I '5") E 8 g i 6 8 0 aoumywsum;

March 28, 1972 J. HEYWOOD ETAL FORMA'IE ESTERS l4 Sheets-Sheet 10 Filed Nov. 21, 1966 kmnEac s Q99 QQQ QQQN Qmm @xmwggm w v m Q9 March 28, 1972 J HEYWQOD ETAL 3,652,656

FQRMATE ESTERS Filed Nov. 21. 1966 14 Sheets-Sheet 11 800 400 200 wavenumber LO 3 5 E i Em LL.

Q QQQ Q- o o n w March 28, 1972 HEYWQQD ETAL 3,652,656

FORMATE ESTERS Filed Nov. 21, 1966 v 14 Sheets-Sheet 12 FIG. 72.

26242220 78 l6 l4 I2 70 8 6 4 2 0 retention time-minutes March 28, 1972 5 J. HEYWQQD ETAL 3,652,656

FOB-MATE ESTERS Filed Nov. 21. 1966 14 Sheets-Sheet 15 WAVELENGTH MICRONS F [G 13 5000 4000 3000 2000 7800 7600 wavenumber o r 0 3 m aounmwsum;

FORMATE ESTERS l4 Sheets-Sheet 14.

Filed Nov. 21. 1966 United States Patent US. Cl. 260-488 R 13 Claims This invention relates to new formate esters, to processes for their preparation and to their use in perfumery.

The Prins reaction, i.e. the acid catalyzed reaction of aldehydes such as formaldehyde and acetaldehyde with olefins, has hitherto been used to prepare many different types of organic compounds including alcohols, diols, monoesters, diesters, m-dioxans and cyclic ethers. A typical example is the application of the Prins reaction to cyclohexene utilising formaldehyde and acetic acid to give 2-acetoxy-methyl-cyclohexyl acetate originally studied by S. Olsen and H. Padberg, Naturforsch. 1 448458 (1946) and subsequently by other workers. This di-ester does not possess properties useful in perfumery products.

It has now been found that when the Prins reaction is applied to an eight membered monocyclic hydrocarbon containing one or two olefinic linkages (i.e. cyclooctene or a cyclooctadiene), optionally carrying one or two methyl groups, utilising formaldehyde and formic acida reaction which has not hitherto been described-a transannular reaction occurs and diformate esters are produced which are useful in perfumery.

According to the present invention, there are provided new diformates which are obtained by reacting an unsaturated hydrocarbon selected from cyclooctene and cyclooctadiene, optionally carrying one or two methyl groups on carbon atoms not forming part of an olefinic linkage, with formaldehyde, or a compound which liberates formaldehyde (for example paraformaldehyde or methylal), in the presence of formic acid, and separating from the reaction mixture the diformate or diformates so produced. The new diformates of the present invention possess very interesting odours and have proved to be very versatile and extremently useful in the formulation of various types of perfumery products. For example, they may be used in formulations in place of orris concrete, an expensive natural perfumery material.

The reaction may be carried out at temperatures between 0 C. and the reflux temperature of the reaction mixture, using formic acid of concentrations between 50% and 100% w./w. in proportions of two equivalents to a considerable excess and formaldehyde, or a compound which liberates formaldehyde (preferably paraformaldehyde), in proportions to give a molecular ratio of unsaturated hydrocarbon to formaldehyde in the range of 1:1 to 1:2. The reaction is preferably carried out in the presence of an excess of formic acid over the two equivalents required to for-m the diformate. Formaldehyde may be introduced into the reaction in the form of an aqueous solution, e.g. a 40% w./v. aqueous solution. Reaction may be elfected in the presence of an antioxidant, such as butylated hydroxy anisole, and an alkali metal formate, for example sodium formate, preferably in a proportion of 2-10% by weight of the formic acid used, in order to limit the extent of undesirable side-reactions such as the addition of formic acid to the olefinic linkages.

The perfumery products of the present invention obtained by the process described above may be a single diformate, as is the case when the unsaturated hydrocarbon starting material is cyclooctene, or mixtures of diformates, as is the case when the unsaturated hydro- 3,652,656 Patented Mar. 28, 1972 ies carbon is a cyclooctadiene, of a complexity which varies according to the starting material. In every instance, however, a crude reaction product is obtained from which a diformate fraction useful in perfumery can be separated. Isolation and purification of the diformate fraction may be effected by conventional methods such as distillation or chromatography.

When the useful diformate fractions are mixtures of two or more diformates, the mixtures may, if desired, be separated into their individual components by the application of known methods for the separation of mixtures, such as fractional distillation, countercurrent distribution, and chromatographic techniques. Mixtures of di-formates may also be converted by hydrolysis (for example using a strong alkali such as potassium hydroxide, in an alcohol containing up to six carbon atoms, preferably methanol) into mixtures of diols, and these mixtures may then be separated into their components by the methods mentioned above, after which the separated diols may be reformylated to give the individual diformates. For the purpose of monitoring the separation of mixtures, the most convenient method has been found to be gas-liquid chromatography, but any other method known to be useful in monitoring the separation of mixtures of organic compounds may also be used, for example tln'n layer chromatography. The structures of individual diformates of the present invention have been identified as hereinafter described by examination of their infra-red spectra, nuclear resonance spectra and mass spectra.

The mixtures of diformates are, however, useful as such and it is normally unnecessary to separate them into their component diformates. Accordingly, it should be understood that the present invention includes within its scope both individual diformates and mixtures of diformates as hereinbefore described which are useful as synthetic perfumery material.

Preferred products of the present invention are those obtained from cyclooctene and cyclooctadiene unsubstituted by methyl groups. Individual products of particular value are:

(a) 4-formoxymethyl-cyclooctyl formate, the single diformate ester which can be isolated from the reaction of cyclooctene with formaldehyde and formic acid,

(b) the diformate fraction C H O isolated from the reaction of cycloocta-1,5-diene with formaldehyde and formic acid, B.P. -l10 C./0.05 to 0.2 mm.'Hg, density 1.1-1.2 g./ml. at 22 C., refractive index 1.47-1.50 at 21 C. in the D line of sodium. The fraction is a complex mixture of diformates, two of which, 3-formoxymethylcyclooct-S-enyl formate and 6-formoxymethyl-cyclooct-3- enyl formate, are particularly important in producing the valuable properties of the mixture, and

(c) the diformate fraction C H O isolated from the reaction of cycloocta-1,3-diene with formaldehyde and formic acid, B.P. -l78 C./22 mm. Hg. The fraction is a mixture of two diformates, 4-formoxymethyl-cyclooct- 2-enyl formate and 2-formoxymethyl-cyclooct-7-enylformate.

According to a further feature of the present invention, new diformate esters may be prepared by the formylation of the corresponding diols. The formylation may be carried out by any known method, for example by the action of formic acid at ambient temperatures. The diol starting materials used in this process may be prepared:

(a) By hydrolysis of a diester other than the diformate, for example the diacetate, prepared by the Prins reaction on cyclooctene or a cyclooctadiene, optionally carrying one or two methyl groups on carbon atoms not forming part of an olefinic linkage, using formaldehyde and an organic acid other than formic acid, optionally in the presence of a strong mineral acid such as perchloric acid.

The hydrolysis of the diester may be carried out by any known method, for example by the action of a strong alkali, such as potassium hydroxide, in an alcohol containing up to 6 carbon atoms, such as methanol.

mixture was refluxed for four hours, during which time it darkened and the paraformaldehyde dissolved. After cooling, the mixture was diluted with water (1.75 litres), and extracted with methylene chloride (700 ml.). The organic (b) By the Prins reaction on a similar unsaturated hy- 5 phase was separated, washed sequentially with Water (250 drocarbon as mentioned in (a) above using formaldehyde m1.) and saturated sodium bicarbonate solution (250 ml.), and a strong mineral acid, such as perchloric acid, and in then dried over magensium sulphate. The desiccant was the absence of any organic acid. removed by filtration, and the filtrate evaporated in vacuo.

Mixtures of diesters other than diformates may also be The residue was distilled through a 6 inch Vigreux column separated and the separations monitored by the methods 10 under vacuum to give the following fractions: mentioned above, after which the separated components Fraction Al: B.P. 55-142 C. at 17 mm. Hg, 67 g. may be converted by known methods into the correspond- Fraction A2: B.P. 142-197" C. at 17 mm. Hg, 200 g. ing diformates. Fraction A2 was redistilled under high vacuum through Diol starting materials which may be formylated are a 6 inch Vigreux column to give the following fractions: 4-hydroxymethyl-cyclooctanol, 3-hydroxymethyl-cyclooct- Fraction B1: B.P. 75 95 C. at 0.06 mm. Hg, 21 g. S-en-l-ol, 6-hydroxymethyl-cycloOct-3-enl-ol, 4-hydroxy- Fraction B2: B.P. 95100 C. at 0.06 mm. Hg, 141 g. methyl-c'yclooct-2-en-l-ol or Z-hydroxymethyl-cyclooct-7- (33% calculated as C I-1 0 en-l-ol, or mixtures of 3-hydroxymethyl-cyclooct-S-en-1-ol Fraction B2 was a colourless liquid possessing a perand 6-hydroxymethyl-cyclooct-3-en-1-ol, or 4-hydroXysistent orris odour with a suggestion of methyl heptine y y and Y Y Y y 20 carbonate, density 11 1.14 8 g./ml., refractive index 11 7-en-1-ol. 1.4865. The infra-red spectrum of this mixture is given in According to another feature of the present invention, FIG. I of the accompanying drawings. saturated diformates within the scope of the present inven- The corresponding diol mixture was prepared by hytion are prepared by the process which comprises reduction drolysis of fraction B2 using potassium hydroxide in methof the corresponding cyclooctenyl diformates by any 25 anol. Examination of this diol mixture by gas-liquid chroknown method for reducing an olefinic linkage without matography (0.5% diethylene glycol succinate polymer affecting a formate ester group, for example by the action stationary phase on Chromosorb G 7080 mesh support; of hydrogen under pressure in the presence of a catalyst column temp. 150 C.) revealed that it consisted of seven such as palladium on charcoal or Raney nickel. The cyclomain components as shown by the chromatogram which octenyl diformate starting material may be 3-formoxyis FIG, II. methyl-cyclooct-S-enyl formate, 6-f rmoxymcthyl-c'yclo- The structure, physical data and method of separation oct-3-enyl formate, 4-fo1'm0xymethyl-cyclooct-Z-enyl forof the diformate components are given in Table ll. Phenylmate, or 2-formoxymethyl-cyclooct-7-enyl formate. urethane derivatives were prepared by known methods By the term known methods as used in this specificafrom the separated diols, themselves prepared either by tion and accompanying claims is meant methods heretohydrolysis of the diformate mixture and separation from fore used or described in the literature. the mixture of the diols obtained, or by hydrolysis of the The following examples illustrate the preparation of the separated diformates obtained from thediformate mixture. new products of the present invention. Hydrolysis in either case is effected with potassium hydrox- EXAMPLE I 40 ide in methanol. The structural formulae of the components were elucidated by nuclear magnetic resonance spec- Paraformaldehyde (93.8 g.) and formic acid (90% troscopy and mass spectroscopy.

w./w. aqueous solution, 350 ml.) were stirred and heated ioifa t iv examination of the various components of j to TefluX, the heating Was pp and y fraction B2 indicated that the components 6 and 7 im- Was added with Vigorous Stirring parted on the mixture of the valuable orris-like odour, over six minutes. The resulting exothermic reaction caused and the process for isolation of these components is given spontaneous refluxing to occur. On complete addition the D in Examples V and VI.

TABLE I Melting point of Approx. Diol phenylpercentpeak in urethane Dilornlate age in Figure deriva- Component Structure component mixture II tive, 0. Method of separation 1 Endo-4-forn1oxy- 6 1 Counteneurrent distributions on low l-formoxyboiling fractions from distillation of QCHZOCOH retreat]- Sfiiii.iiiiiiily fiiPdfiiisifi 11 O O O octane.

2 raster- 3 2 iftfitiiiitiiitiiiintltlttliiiitt5% clooct-5-onyl the mixture, using AgN O3 impregnated O C OH formate. silica gel column.

3 HO O O Endo-2-iorinoxy- 14 3 168-169 Counter-current distributions on certain i exo-fi-iormoxyhydrolysed high-boiliug fractions from methyl-cis-bithe distillation of the ester mixture, cycl0-[3.3.0.] followed by column chromatography I octane. on sillca gel.

4 HOCO Exo-2-iorrnoxy- 22 4 Il7o Counter-current distributions on diol Y eudo-6-ionnoxymixture.

methyl-eisbicyc1o[3.3.0.] octane.

l CHzOCOH Melting point of Approx. Diol phenylpercentpeak in urethane Dn'ormate age in Figure deriva- Component Structure component mixture II tive, 0. Method of separation 5 Endo-S-formoxy- 18 5 178-179 Counter-current distributions and col- HO 0 H endo-2-iormoxyumn chromatographies on a hydrolysed methyl-bicycle main distillation fraction from [3.2.1.]octane. ficient fractionation of ester mixture. CHzO C O H 6 CHQO O OH 3-formoxymethyl 14 6 Chromatography on AgNOa impregcyclooct--enyl nated silica-gel column of a high-boiling formate (main fraction from efiicient fractionation of l component). ester mixture.

0 O O H 7 CH2) COH fi-formoxymethyl 12 7 103 Alternate counter-current distributions cyclooet3-enyl and column chromatographies on hydro formats. lysed residue from eflicient fractionation of ester mixture.

EXAMPLE II Fraction A4: B.P. 140-170 C. at 10 mm. Hg, 35.5 g.

Paraformaldehyde (451 g.) and formic acid (98- 100% w./w.; 2,500 ml.) were heated together under reflux until all solid had dissolved. The solution was cooled to room temperature and cis,cis-cycloocta-1,5-diene (1080 g.) Was added. The mixture was stirred vigorously for three days at room temperature, during which time the heterogeneous mixture became homogeneous. Excess formic acid was removed in vacuo keeping the temperature below 40 C. and the residue distilled to give the following fractions:

Fraction Al: B.P. below 90 C. at 0.5 mm. Hg, 720 g.

Fraction A2: B.P. 90126 C. at 0.5 mm. Hg, 1070 g.

Fraction A2 was redistilled through a cm. vacuumjacketed Widmer column to give the following fractions:

Fraction B1: B.P. below 102 C. at 0.2 mm. Hg, 90 g.

Fraction B2: B.P. 102-109 C. at 0.2 mm. Hg, 787 g., 37% yield, calculated as C H O Fraction B2 had an identical odour to that of fraction 4 B2 in Example I.

EXAMPLE -III A mixture of cis,cis-cycloocta-1,5-diene (108 g.), formic acid (90% w./w.; 350 ml.) and aqueous formaldehyde w./v.; ml.) was stirred for 5 days at room temperature. The resultant heterogeneous mixture was treated by the method used in Example I to give a fraction B.P. 100l05 C. at 0.2 mm. Hg, 51 g., 25% yield calculated as C H O This fraction had an identical odour to that of fraction B2 in Example I.

EXAMPLE IV A mixture of cis,cis-cycloocta-1,5-diene (44 g.), paraformaldehyde (24 g.), w./w. formic acid ml.), anhydrous sodium formate (5 g.) and butylated hydroxy anisole (0.5 g.) was heated at reflux for 8 hours. The reaction mixture was allowed to cool to below 30 C. and poured into water (500 ml.). The separation of organic material was facilitated by the addition of methylene chlo ride (200 ml.). The methylene chloride solution was sequentially washed with water (2X 250 ml.), saturated aqueous sodium bicarbonate solution, (250 ml.), dried over magnesium sulphate, filtered, and evaporated from a steam bath at atmospheric pressure. The crude product obtained was fractionally distilled through a inch diameter, 6 inch Vigreux column to give the following fractions:

Fraction A1: B.P. 40-70 C. at 10 mm. Hg, 3.0g.

Fraction A2: B.P. 80-100 C. at 10 mm. Hg, 4.2 g.

Fraction A3: B.P. -138 C. at 10 mm. Hg, 11.8 g.

Fraction A5: B.P. 170-220 C. at 10 mm. Hg, 11.2 g.

Fraction A4 was redistilled to give a fraction B.P. 95- 97 C. at 0.1 mm. Hg, 30.0 g., 37% yield calculated as C H O This fraction had an identical odour to that of fraction B2 in Example I.

EXAMPLE V A sample of the product (540 g.) obtained as fraction B2 in Example I was partitioned between n-heptane and 50% aqueous methanol in five portions using a countercurrent technique of 5 cycles, 5 funnels and 1 litre phase volumes. The heptane-soluble material was recovered by evaporation of the solvent, yielding 350 g. material. This material was distilled from a three necked round-bottomed flask fitted with an air bleed and thermometer and employing a 1.5 metre heated glass column packed with knitted monel alloy. The reflux head, fitted with a vertical Liebig condenser, had a solenoid-operated pulsating valve to control reflux ratio.

A total of 271 g. of distillate was obtained in 34 arbitrary fractions of approximately 8 g. each. Fraction 29, B.P. 1154-1158 C. at 1.5 mm. Hg, was shown by gas-liquid chromatography on diethyleneglycol succinate polymer to contain approximately 30% of component 6 described in Table I, without appreciable amounts of any other unsaturated materials, i.e. components 2 and 7 described in Table I.

400 mg. of fraction 29 was therefore chromatographed on a silver nitrate impregnated silica gel column. The column packing was prepared by mixing chromatography grade silica gel g.) with silver nitrate solution (10% W./v.; 230 ml.), drying, and activating the packing overnight in an oven at 90 C. The column, employing 20 g. of the packing, was made up in a 25 ml. burette (1 cm. diameter). A 3:1 mixture of diethyl ether and n-hexene was used as eluant. The following fractions were collected and evaporated to yield diformate material:

(a) First 16 ml. giving saturated material (250 mg.)

(b) Next 8 ml., giving a mixture of saturated and unsaturated material (50 mg.)

(c) Next ml., giving predominantly unsaturated material (100 mg.)

400 mg. of material obtained in the same manner as (0) above was rechromatographed on a Florisil column, eluting with methylene chloride. The first 9 ml. of eluent was discarded, and the next 20 ml. yielded 250 mg of material.

950 mg. of material obtained by the same procedure was distilled under high vacuum in a bulb tube to give 350 mg. of product, boiling at an air bath temperature of 80-110 C. under 0.006 mm. Hg; the infra-red spectrum of this fraction is given in FIG. III.

Gas-liquid chromatography of this product, and of the diol obtained on hydrolysis of a portion of this product, indicated the presence of two components. The major diester component possessed a pleasant violet-orris odour, and was shown by nuclear magnetic resonance spectroscopy (FIG. IV) to be 3-formoxymethyl-cyclooct-S-enyl formate.

EXAMPLE VI Fraction B2 of Example II (787 g.) was distilled using the apparatus described in Example V. Thirty arbitrary fractions were collected of approximately ml. each; 90 g. of residue remained. This residue was shown by gasliquid chromatography to contain a large proportion of difiormate material, as well as some high-boiling byproducts. It was hydrolysed by methanolic potassium hydroxide to give the corresponding diol material together with the high-boiling by-products. Gas liquid chromatography of the diol showed it to be almost exclusively the diol corresponding to component 7 in Table I.

Purification of this diol was effected by a sequence comprising alternate column chromatography separations and manual counter-current distributions, the final purification being effected by an automatic counter-current distribution using 56 cycles, followed by three successive column chromatography separations.

The distribution experiments, both manual and automatic, employed a methylene chloride-water system, material being recovered from the aqueous layer by saturation with sodium chloride and extraction with an equal volume of ethyl acetate. Column chromatography was carried out using 33 x 2.5 cm. columns of chromatography grade silica gel. A graded elution technique was used, starting with diethyl ether containing 1% ethanol, and increasing the proportion of ethanol to 20%. The processes were monitored by thin layer and gas-liquid chromatography.

15 g. of crude diol yielded 0.8 g. of pure diol corresponding to component 7 of Table I.

Material obtained in this manner was converted to a crystalline phenylurethane, which, after two recrystallisations from glacial acetic acid, had a melting point of 193 C. Elemental microanalysis gave the following results:

C H N O requires (percent): C, 70.1; H, 6.6; N, 7.1. Found (percent): C, 70.4; H, 6.6; N, 7.2.

800 mg. of pure diol were converted back to the diformate by the action of 98-100% w./w. formic acid at room temperature to give 6300 mg. of product. This product was distilled in a bulb tube at 120 C. (air bath temperature) under 0.2 mm. Hg. The diformate distillate possessed a pleasant woody-orris-like odour, and was shown by nuclear magnetic resonance spectroscopy (FIG. V) to be 6-formoxymethylcyclooct-3-enyl formate.

EXAMPLE VII Paraformaldehyde (18 g.) and formic acid (98-100%; 100 ml.) were heated together with stirring in a 500 ml. conical flask on a hotplate-magnetic stirrer and allowed to reflux until all of the paraformaldehyde had dissolved (10 min). The solution was cooled to room temperature and cyclo-octene (redistilled; 44 g.) was added, giving a heterogeneous mixture. The mixture was stirred at room temperature for 2 days. The excess formic acid was removed by vacuum distillation on a rotary evaporator below 30 C. The residue was dissolved in methylene chloride (150 ml.) and washed once with water (75 ml.) and once with saturated sodium bicarbonate solution (75 ml.). The organic phase was dried over magnesium sulphate and filtered. After removal of the organic solvent on the rotary evaporator, and low-boiling material at water pump pressure by conventional distillation, the remainder was distilled using a high vacuum pump giving only a moderately high vacuum.

The following broad fractions were collected:

Fraction A1:B.P. -95 C. at 4 mm. Hg, 9 g. Fraction A2:B.P. -130 C. at 4 mm. Hg, 6 g. Fraction A3:B.P. -l44 C. at 4 mm. Hg, 41 g.

Redistillation of the third fraction at water pump pressure (11 mm.) gave:

Fraction B1:B.P. ISO-156 C. at 11 mm. Hg, 6 g. Fraction B2:B.P. 156-l59 C. at 11 mm. Hg, 33 g., 39%

calculated as CHI-11804.

Fraction B2 had a refractive index of n =1.4769, and an odour suggestive of violet with a persistent orrislike undertone. It was shown by gas-liquid chromatography (0.5% diethylene glycol succinate polymer stationary phase on Chromosorb G. 70-80 mesh support; column temp. C.) to be substantially a single substance (FIG. VI), and infra-red spectroscopy (FIG. VII), nuclear magnetic resonance spectroscopy (FIG. VIII) and mass spectroscopy showed it to be 4-formoxymethylcyclooctyl formate.

The same product is obtained in similar yield when the reactants are refluxed together for four hours and subjected to the same working up procedure.

A sample of fraction B2 was converted to the corresponding diol by hydrolysis in methanolic potassium hydroxide and then converted to a crystalline phenylurethane which, after three recrystallisations from benzene had a melting point of 146.5-147 C. The infra-red spectrum of this derivative is given in FIG. IX. Elemental microanalysis gave the following results:

C H N O (percent): C, 69.7; H, 7.06; N, 7.06. Found (percent): C, 69.7; H, 7.0; N, 7.1.

This phenylurethane had an identical infra-red spectrum (FIGS. IX and X) to, and produced no depression of melting point when mixed with, a phenylurethene prepared by the following procedure:

A sample of the diol corresponding to 6-formoxymethyl-cyclooct-3-enyl formate, prepared as in Example VI, was hydrogenated in methanol using 5% palladium on charcoal catalyst at 90 psi. and room temperature for three hours. The methanol was evaporated from the filtered reaction mixture and the reduced diol converted to its phenylurethane which, after two recrystallizations from benzene, had a melting point of 144-146 C. The infra-red spectrum of this material is given in FIG. X.

EXAMPLE VIII Paraformaldehyde (4.5 g.) and formic acid (98-l00% w./w.; 25 ml.) were refluxed together until all of the solid had dissolved. The solution was cooled to room temperature and treated with cycloocta-1,3-diene (10.8 g.; prepared according to French Pat. No. 1,337,899). The heterogeneous mixture was stirred for three days at room temperature, during which time it becomes homogeneous. The clear solution was poured into distilled water (100 ml.), and extracted with methylene chloride (40 ml.). The organic extract was sequentially washed with water (15 ml.), saturated sodium bicarbonate (15 ml.) and water (15 ml.). After drying over magnesium sulphate the solvent was evaporated and the residue distilled to give the following fractions:

Fraction A1: B.P. below 140 C. at 15 mm. Hg, 0.7 g. Fraction A2: B.P. 1140-158 C. at 15 mm. Hg, 1.3 g. Fraction A3: B.P. 158-168 C. at 15 mm. Hg, 13.7 g.

Fraction A3 was redistilled and the following fractions claimed:

Fraction B1: B.P. 158-170 C. at 22 mm. Hg, 2.7 g. Fraction B2: B.P. -178 C. at 22 mm. Hg, 10.4 g.,

49% yield calculated as (3111 11604.

Fraction 132 had a similar odour to that of fraction B2 in Example I. The infra-red spectrum of this fraction is given in FIG. XI. 10.0 g. of this fraction were bydrolysed by the action of methanolic potassium hydroxide to give, on distillation, the corresponding diol (7.0 g.), B.P. 115-125 C. at 0.05 mm. Hg. This diol was shown by gas-liquid chromatography (FIG. XII-0.5% diethyl eneglycol succinate polymer stationary phase on Chromosorb G 70-80 mesh support; column temp. 150 C.) to consist of two components in a 3:1 ratio, neither of which occurred in the diol mixture corresponding to fraction B2 of Example I. 2.0 g. of this diol were hydrogenated in methanol at 85 C. and 200 p.s.i. using Raney nickel catalyst. Gas-liquid chromatography of the product showed that the major component was identical to the diol obtained by the hydrolysis of fraction B2 of Example VII. The diol was converted to its phenylurethane which, after three recrystallisations from benzene, had a melting point of 144-146C., undepressed by admixture with the phenylurethane of Example VII. The infra-red spectra of the two phenylurethanes were identical (FIGS. XIII and 1X). Nuclear magnetic resonance spectra (FIG. XIV), and mass spectra, show that the major component of fraction B2 is 4formoxymethyl-cyclooct-2-enyl formate and the minor component is 2-formoxymethyl-cyclooct- 7-enyl formate.

EXAMPLE IX The diformate fraction B2 of Example VIII g.) was hydrogenated catalytically in ethereal solution at room temperature and 200 p.s.i. pressure employing platinum on carbon as catalyst. Filtration, evaporation of the solvent and distillation of the residue yielded 4.5 g. of product shown by gas-liquid chromatography to contain two components, the major one identical with the product fraction B2 of Example VII and having similar properties.

EXAMPLE X A mixture of paraformaldehyde (45 g.), glacial acetic acid (200 ml.) and aqueous perchloric acid (1.0 ml.; 72% w./w.) was refluxed with stirring until all solid material had dissolved. Cis,cis-cycloocta-1,5-diene (108 g.) was then added dropwise over 20 minutes, and the refluxing continued for a further 30 minutes. The solution was cooled and anhydrous sodium acetate (5 g.) added to neutralise the perchloric acid. The reaction mixture was worked up in the same way as Example I and the product distilled to give the following fractions:

Fraction A1: B.P. 4070 C. at 15 mm. Hg, 20 g. Fraction A2: B.P. 70l40 C. at 15 mm. Hg, 19 g. Fraction A3: B.P. 140-200 C. at 15 mm. Hg, 56 g. Fraction A4: B.P. 200-240 C. at 15 mm. Hg, 16 g.

Fraction A3 was redistilled to give the following fractions:

Fraction B1: B.P. below 105 C. at 0.1 mm. Hg, g. Fraction B2: B.P. 105-112 C. at 0.1 mm. Hg, 36 g.,

yield calculated as C H O The product has a faint, sweet odour, typical of acetate esters.

Fraction B2 (12.6 g.) was hydrolysed to the corresponding diol mixture using methanolic potassium hydroxide. The crude diol (8.1 g.; 96%) was shown by gasliquid chromatography to contain the same seven major diol components in approximately the same proportions as the diol mixture prepared from fraction B2 of Example I.

4.05 g. of the diol obtained from fraction B2 was dissolved in 98100% formic acid (40 ml.) and allowed to stand at room temperature for 24 hours. The solution became dark brown. The product was isolated, using the procedure described in Example I, distillation yielding 3.24 g. (64%) of diformate, B.P. 92-94 C. at 0.09 mm. Hg, which possessed an identical odour to that of fraction B2 of Example I.

The present invention includes within its scope a compound perfume base comprising a plurality of odiferous principles, one of which is a diformate or a mixture of diformates of the present invention. Such compound perfume bases may be prepared by known methods, and may include conventional perfume materials such as natural products, e.g. Oil of Sandalwood E. India, Oil of Clary Sage, Oil of Bergamot, Jasmin absolute and Violet Leaf absolute, and synthetic products, e.g. Rhodinol and the various aldehydes used in perfumery, including undecylenic aldehyde and methyl nonyl acetaldehyde.

Compound perfume bases according to the present invention may, for example, be used to perfume materials such as soap and other detergents, and talcum powder.

The following example illustrates the preparation of new perfumery compositions according to the present invention.

EXAMPLE XI A compound perfume base of the lily type was prepared having the following composition:

Part by weight Linalool ex Bois de Rose 40.0 Oil of bergamot 20.0 Neroli bigarard 0.5 Oil ylang ylang bourbon extra 0.3 Oil of Cananga 0.8 Hydroxycitronellal extra prime 12.0 Lilac base 6.0 Heliotropine 2.0 Diformate fraction B2 of Example I 10.0 Musk ambrette 2.0 Terpineol extra prime 6.4

In this composition the diformate fraction replaced Oil Orris Concrete in a conventional composition, and the product possessed a more floral note than the original.

In other experimental work, diformates of the present invention have been used in aromatic compositions in amount ranging from 0.5% to 70% by Weight. They exert their effect even at low concentrations, and at high concentrations do not produce any unpleasant odours.

We claim:

1. The diformate fraction of empirical formula C H O obtained by the reaction of cycloocta-l,5-diene with formaldehyde or paraformaldehyde in the presence of formic acid, said fraction having a boiling point of -110 C./0.05 to 0.2 mm. Hg, a density of 1.1-1.2 g./ml. at 22 C., and refractive index 1.47-1.50 at 21 C. in the D line of sodium.

2. The diformate fraction of empirical formula C H O obtained by the reaction of cycloocta-1,3-diene with formaldehyde or paraformaldehyde in the presence of formic acid, said fraction having a boiling point of -178 C./22 mm. Hg and consisting essentially of 4- formoxymethyl-cyclooct-2-enyl formate and 2-formoxymethyl-cyclooct-7-enyl formate.

3. The diformate fraction of empirical formula C H O obtained by the reaction of cyclooctene with formaldehyde or paraformaldehyde in the presence of formic acid, said fraction having a boiling point of 156 159 C./l1 mm. Hg, and refractive index 1.4769 at 21 C. in the D line of sodium and consisting essentially of 4-formoxymethyl-cyclooctyl-formate.

4. A member of the class consisting of 4-formoxymethyl-cyclooctyl formate, 3-formoxymethyl-cyclooct-S- enyl formate, 6-formoxymethyl-cyclooct-3-enyl formate, 4-formoxymethy1-cyclooct-2-enyl formate and 2-formoxymethyl-cyclooct-7-enyl formate.

5. Process for the production of a mixture of diformates having valuable olfactory properties and containing a 4 formoxymethyl-cyclooctyl formate or a 6- formoxymethylcyclooct-3-enyl formate which comprises reacting an unsaturated hydrocarbon selected from the class consisting of cyclooctene, 1,5-cyclooctadiene, and cyclooctene and 1,5-cyclooctadiene carrying at most two methyl groups, the methyl groups being on carbon atoms not forming part of an olefinic linkage, with formaldehyde, or a compound which liberates formaldehyde under the reaction conditions, in the presence of formic acid, at a temperature between C. and the reflux temperature of the reaction mixture, and separating from the reaction mixture the said diformate mixture so produced.

6. Process according to claim wherein the compound which liberates formaldehyde is paraformaldehyde or methylal.

7. Process according to claim 5 in which the molecular ratio of unsaturated hydrocarbon to formaldehyde in the reaction mixture is in the range 1:1 to 1:2, and at least two molecular equivalents of formic acid are present for each mole of unsaturated hydrocarbon reactant.

8. Process according to claim 5 in which the reaction is carried out in the presence of an antioxidant and an 20 alkali metal formate.

9. Process for the production of a mixture of diformates having valuable olfactory properties and containing 4-formoxymethy1cyclooctyl formate or 6-formoxymethylcyclooct-3-enyl formate which comprises reacting an unsaturated hydrocarbon selected from the class consisting of cyclooctene and 1,5-cyclooctadiene with formaldehyde, or a compound which liberates formaldehyde under the reaction conditions, in the presence of formic acid at a temperature between 0 C. and the reflux temperature of the reaction mixture, and separating from the reaction mixture the said diformate mixture so produced.

10. Process according to claim 9 wherein the compound which liberates formaldehyde is paraforma'ldehyde or methylal.

11. Process according to claim 9 in which the molecu lar ratio of unsaturated hydrocarbon to formaldehyde in the reaction mixture is in the range 1:1 to 1:2, and at least two molecular equivalents of formic acid are present for each mole of unsaturated hydrocarbon reactant.

12. Process according to claim 5 in which the unsaturated hydrocarbon reactant is cycloocta-2,5-diene.

13. Process according to claim 9 in which the unsaturated hydrocarbon reactant is cyclooctene.

References Cited UNITED STATES PATENTS 3,128,304 4/1964 Lafont 260497 3,366,700 1/1968 Ziegenbein et a1. 260-488 3,433,828 3/1969 Norell 260-488 OTHER REFERENCES S. Olsen et al., Naturforsch 1, 448-458 (1946).

LORRAINE A. WEINBERGER, Primary Examiner V. GARNER, Assistant Examiner US. Cl. X.R. 

1. THE DIFORMATE FRACTION OF IMPRIRICAL FORMULA C1H16O4 OBTAINED BY THE REACTION OF CYCLOOCTA-1,5-DIENE WITH FORMALDEHYDE OR PARAFORMALDEHYDE IN THE PRESENCE OF FORMIC ACID, SAID FRACTION HAVING A BOILING POINT OF 90-110* C./0.05 TO 0.2MM. HG, A DENSITY OF 1.1-1.2 G/ML. AT 22* C., AND REFRACTIVE INDEX 1.47-1.50 AT 21*C. IN THE D LINE OF SODIUM. 